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A Clinical Study to Find Out if Macitentan is Effective and Safe in Japanese Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

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ClinicalTrials.gov Identifier: NCT03809650
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : October 2, 2019
Sponsor:
Collaborators:
EPS Corporation
Imepro Inc.
General Laboratory, BML, Inc.
Mitsubishi Logistics Corporation
Information provided by (Responsible Party):
Actelion

Brief Summary:
The endothelin receptor antagonist macitentan showed significant improvement compared with placebo in pulmonary vascular resistance (PVR) and 6-minute walking distance (6MWD) in inoperable CTEPH patients in the phase II MERIT-1 trial (AC-055E201, NCT02021292). However, in the MERIT-1 trial Japanese patients were not included. Therefore, in line with Japan's medical environment, this phase III study is to confirm the efficacy and safety of macitentan in Japanese CTEPH patients.

Condition or disease Intervention/treatment Phase
Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Drug: macitentan 10 mg Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Open-label, Single Arm, Phase III Study to Assess the Efficacy and Safety of Macitentan (ACT-064992) in Subjects With Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Actual Study Start Date : January 8, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: Open-label treatment period
oral administration of macitentan 10 mg once daily
Drug: macitentan 10 mg
macitentan 10 mg, film-coated tablet, oral use
Other Name: ACT-064992, Opsumit®




Primary Outcome Measures :
  1. Evaluate the ratio in pulmonary vascular resistance (PVR) at rest from baseline to Week 16 [ Time Frame: From Baseline to Week 16 ]
    The resistance in the artery carrying blood to the lungs is called PVR. The PVR is the resistance in the artery carrying blood to the lungs and that has to be overcome by the right ventricle in heart in order to let blood flow to the lungs occur. The ratio in PVR at rest indicates the efficacy of macitentan in patients with CTEPH. The ratio in PVR at rest is calculated as PVR at Week 16 divided by baseline PVR. The ratio in PVR at rest from baseline to Week 16 of administration of macitentan is evaluated in subjects with CTEPH who are not indicated for pulmonary endarterectomy (PEA) and/or subjects who have postoperative persistent or recurrent pulmonary hypertension (PH) after PEA and/or balloon pulmonary angioplasty (BPA).


Secondary Outcome Measures :
  1. Change from baseline to Week 16 in PVR at rest [ Time Frame: From baseline to Week 16 ]
    The PVR at rest will be calculated to evaluate the change in PVR at rest from pre-dosing (baseline) to post-dosing (Week 16).

  2. Change from baseline to Week 16 in pulmonary vascular resistance index (PVRI) at rest [ Time Frame: From baseline to Week 16 ]
    The indexed PVR (PVRI) at rest will be calculated to evaluate the change in PVRI at rest from pre-dosing (baseline) to post-dosing (Week 16).

  3. Change from baseline to Week 24 in 6-minute walk distance (6MWD) [ Time Frame: From baseline to Week 24 ]
    The purpose of the 6-minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. This endpoint evaluates the change in 6MWD from pre-dosing (baseline) to post-dosing (Week 24).

  4. Change from baseline to Week 24 in Borg dyspnea index [ Time Frame: From baseline to Week 24 ]
    The Borg dyspnea index rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the Borg dyspnea index indicates an improvement. This endpoint evaluates the change in the Borg dyspnea index assessed at the end of measuring the 6MWD from pre-dosing (baseline) to post-dosing (Week 24).

  5. Change from baseline to Week 24 in WHO functional class (WHO FC) [ Time Frame: From baseline to Week 24 ]
    This endpoint evaluates the change of WHO functional class from pre-dosing (baseline) to post-dosing (Week 24). Class I: no symptoms with exercise or at rest. No limitation of activity. Class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). Class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. Class IV: symptoms at rest (e.g. dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms. Patients in class IV manifest signs of right heart failure.



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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent to participate in the study obtained from the subject or legal representative a) prior to initiation of any study mandated procedure
  • Japanese subjects who have been diagnosed as having CTEPH:

    1. Subjects who have not undergone balloon pulmonary angioplasty (BPA) and for whom the investigator determines not to implement pulmonary endarterectomy (PEA) at the time of the acquisition of informed consent due to the organized thrombosis localized in the peripheral regions, high risk (complications, old age, etc.) or for any other reasons.
    2. Subjects who have postoperative persistent or recurrent pulmonary hypertension (PH) after undergoing pulmonary endarterectomy (PEA) and/or BPA.
  • PH subjects whose WHO FC is I to IV
  • 6MWD measured during the screening period ranges from 150 m to 450 m
  • Subjects who meet the following conditions according to the right heart catheterization (RHC) performed during the screening period or within 8 weeks before the acquisition of the informed consent:

    1. Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg
    2. Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg (if PAWP cannot be measured or the value of PAWP is not reliable, left ventricular end-diastolic pressure ≤ 13 mmHg)
    3. Resting PVR ≥ 400 dyn*sec/cm5
  • Subjects treated with anti-coagulation agents, unfractionated heparin or low molecular weight heparin at least 90 days prior to RHC at baseline
  • Women with childbearing potential with negative serum pregnancy test results and able to follow the appropriate contraceptive methods from the date of starting the study drug administration up to 30 days after the discontinuation or completion of the study drug administration. Fertile male subjects able to use condom during the same period.

Exclusion Criteria:

  • BPA within 90 days prior to undergoing baseline RHC
  • PEA within 180 days prior to undergoing baseline RHC
  • Subjects with unstable pulmonary hemodynamics who have postoperative persistent or recurrent PH after undergoing PEA and/or BPA
  • Recurrent thromboembolism undergoing treatment with oral anti-coagulation agents
  • Symptomatic acute pulmonary embolism within 180 days prior to the start of study drug administration
  • Known moderate-to-severe restrictive lung disease or obstructive lung disease or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema)
  • Acute myocardial infarction during Screening period
  • Severe liver impairment.
  • Systolic blood pressure (SBP) < 90 mmHg at screening.
  • Any known factor or disease that may interfere with treatment compliance or full participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03809650


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Japan
Fukushima Medical University Hospital Recruiting
Fukushima, Japan, 960-1247
Kagoshima University Hospital Recruiting
Kagoshima, Japan, 890-8520
Nara Medical University Hospital Recruiting
Kashihara, Japan, 634-8522
Kokura Kinen Hospital Recruiting
Kitakyushu, Japan, 802-8555
Kobe University Hospital Recruiting
Kobe, Japan, 650-0017
Saitama Cardiovascular and Respiratory Center Recruiting
Kumagaya, Japan, 360-0197
Kure Kyosai Hospital Recruiting
Kure, Japan, 737-8505
Kurume University Hospital Recruiting
Kurume, Japan, 830-0011
Toho University Ohashi Medical Center Recruiting
Meguro-ku, Japan, 153-8515
IIUHW Mita Hospital Recruiting
Minato-ku, Japan, 108-8329
Kyorin University Hospital Recruiting
Mitaka, Japan, 181-8611
Nagasaki University Hospital Recruiting
Nagasaki, Japan, 852-8501
National Hospital Organization Okayama Medical Center Recruiting
Okayama, Japan, 701-1192
Sapporo Medical University Hospital Recruiting
Sapporo, Japan, 060-8543
Hokkaido University Hospital Recruiting
Sapporo, Japan, 060-8648
Sasebo City General Hospital Recruiting
Sasebo, Japan, 857-8511
National Cerebral and Cardiovascular Center Hospital Recruiting
Suita, Japan, 565-8565
Mie University Hospital Recruiting
Tsu, Japan, 514-8507
Yamagata University Hospital Recruiting
Yamagata, Japan, 990-0828
Yokohama City University Hospital Recruiting
Yokohama, Japan, 236-0004
Sponsors and Collaborators
Actelion
EPS Corporation
Imepro Inc.
General Laboratory, BML, Inc.
Mitsubishi Logistics Corporation
Investigators
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Study Director: Yoshinari Yokoyama, PhD Actelion Japan

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Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT03809650     History of Changes
Other Study ID Numbers: AC-055E301
First Posted: January 18, 2019    Key Record Dates
Last Update Posted: October 2, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials\transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Actelion:
CTEPH
chronic thromboembolic pulmonary hypertension
macitentan
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Macitentan
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Endothelin B Receptor Antagonists